A well-known inflammatory protein spawns an enzyme that inactivates two tumor-suppressing
genes, ultimately triggering production of new blood vessels to nourish breast cancer
cells, researchers at the University of Texas M. D. Anderson Cancer Center report in the
August edition of the journal Cell.

Inflammation from bacterial infections is linked to preterm births and deaths, according
to researchers from Case Western Reserve University's School of Dental Medicine and the
Case School of Medicine. They found if receptors responding to the presence of dead or
living bacteria in the placentas of mice can be blocked, the number of preterm deaths will
decline by nearly half.

Researchers recently identified how a regulatory protein called Bcl-3 helps to control the
body's inflammation response to infection by interfering a critical biochemical process
called ubiquitination. Their findings open new avenues for developing therapies to treat
such diseases as sepsis, diabetes and rheumatoid arthritis.

the evidence is accumulating on how bad stress is for health. Chronic stress can intensify
inflammation and increase a persons risk for developing central nervous system
infections, neurodegenerative diseases, like multiple sclerosis (MS), and other
inflammatory diseases, say researchers presenting at the 115th Annual Convention of the
American Psychological Association (APA).

In a study to be published in the January 09 issue of Experimental Biology and Medicine,
Hoover-Plow and co-workers in seeking to define a role of apo(a) in leukocyte recruitment
have identified a novel activity of apo(a) apolipoprotein that may function as a natural
and cell specific suppressor of the inflammatory response in vivo. In addition, a
mechanism for this novel function of apo(a) was also identified: its selective regulation
of cytokine production. These effects of apo(a) are independent of its molecular mimicry
of Plg. Lipoprotein(a) (Lp(a)) is similar to low density lipoprotein (LDL), but contains
an additional apolipoprotein, apo(a). Numerous clinical studies conducted over the past 40
years have identified Lp(a) as a risk factor independent from LDL for a variety of
cardiovascular pathologies. Much of the focus of apo(a) pathogenic activities has centered
on its strong resemblance to plasminogen, the zymogen for plasmin, the primary enzyme for
blood clot degradation. In addition to its important role in clot lysis, plasmin is
required for leukocyte recruitment in inflammation. While several in vitro studies have
demonstrated the interference of apo(a) in plasminogen leukocyte recruitment, evidence for
this in vivo has been lacking.

Results suggest that traffic emission sources of OCpri and quasi-ultrafine particles lead
to increased systemic inflammation and platelet activation and decreased antioxidant
enzyme activity in elderly people with CAD.

Scientists have discovered that a lipid known to protect the heart from inflammation and
to cause skin allergic reactions also reduces inflammation of the kidneys. The discovery
could help devise new ways of treating inflammatory kidney diseases. The lipid, called
sphingosylphosphorylcholine (SPC), has been shown to cause an increase in urine production
in the kidneys and an abnormal accumulation of salt in the urine. But how SPC works in the
kidneys is not completely understood. Andrea Huwiler and colleagues examined the various
proteins activated by SPC in kidney cells and showed for the first time that SPC triggers
proteins known to reduce inflammation. Although more details will be needed to understand
how these proteins and how SPC may interact with other anti-inflammatory proteins 
such as transforming growth factor beta  SPC may be useful in the treatment of
chronic inflammatory and fibrotic diseases of the kidneys, the scientists concluded.

Researchers have uncovered why some dietary fats, specifically long-chain fats, such as
oleic acid (found in olive oil), are more prone to induce inflammation. Long-chain fats,
it turns out, promote increased intestinal absorption of pro-inflammatory bacterial
molecules called lipopolysaccharides (LPS). This study appears in the January issue of
JLR.While dietary fats that have short chains (such as those found in milk and cheese
products) can be absorbed directly into the bloodstream from the intestines, long-chain
fats need to be first packaged by the intestinal cells into particles known as
chylomicrons (large complexes similar to HDL and LDL particles). Erik Eckhardt and
colleagues at the University of Kentucky wondered whether some unwanted LPS particles,
routinely shed by the bacteria that inhabit the human gut, might also be sneaking in the
chylomicrons. Their hypothesis turned out to be correct; when they treated cultured human
intestinal cells with oleic acid they observed significant secretion of LPS together with
the chylomicron particles, a phenomenon that was not observed when the cells were treated
with short-chain butyric acid. Similar findings were found in mouse studies; high amounts
of dietary oleic acid, but not butyric acid, promoted significant absorption of LPS into
the blood and lymph nodes and subsequent expression of inflammatory genes. Eckhardt and
colleagues believe these findings may pave the way for future therapies for Crohn's
disease and other inflammatory bowel disorders. In addition, they note that this study
once again highlights the importance of the diverse bacteria that call our intestines
home.

Scientists have discovered that a lipid known to protect the heart from inflammation and
to cause skin allergic reactions also reduces inflammation of the kidneys. The discovery
could help devise new ways of treating inflammatory kidney diseases.

The ability of the body's cells to correctly receive and convey signals is crucial to good
health. Lipids, or fats, play a critical role in this regulation by providing spaces for
proteins to gather and network. They are helped in this process by protein molecules
called lipid binding domains. Understanding how these domains work may open up new targets
of opportunity for drug development to treat illnesses such as cancer, diabetes and
various inflammatory diseases. Studying lipid binding domains is a specialty of Wonhwa
Cho, distinguished professor of chemistry at the University of Illinois at Chicago. In two
recently released papers appearing in the EMBO Journal and the Journal of Biological
Chemistry, Cho and his associates describe mechanisms by which a particular binding domain
-- the PX or "Phox" -- recognize specific lipids and interact with cell
membranes to modulate functions.

Discovery of a new signaling
mechanism may lead to novel anti-inflammatory therapy

A team of researchers at the University of California, San Diego School of Medicine has
uncovered a new signaling mechanism used to activate protein kinases that are critical for
the body's inflammatory response.

Researchers led by Drs. Lillian Maggio-Price and Brian Iritani at The University of
Washington found that mice that lack the immune inhibitory molecule Smad3 are acutely
sensitive to both bacterially-induced inflammation and cancer. They report these findings
in the January 2009 issue of The American Journal of Pathology. Bacteria contribute to the
development of certain cancers, in some measure, by stimulating chronic inflammation.
Absence of a molecule that inhibits inflammation, Smad3, may therefore increase
susceptibility to colon cancer. To examine whether Smad3 signaling contributes to
development of colon cancer, Maggio-Price et al examined mice deficient in Smad3 that lack
of adaptive immune responses. They found that these mice are acutely sensitive to
bacterially-induced inflammation and cancer due to both deficient T regulatory cell
function and increased expression of proinflammatory cytokines. Through increased
expression of both pro-oncogenic and anti-apoptotic proteins, epithelial cells in colonic
tissues underwent both enhanced proliferation and survival. "That the inflammatory
response to microorganisms is a key event in these results reveals important
'tumor-suppressive' functions for Smad3 in T effector cells, T regulatory cells, and
intestinal epithelial cells, all of which may normally limit the development of colon
cancer in response to bacterial inflammation," explains the groups led by Dr.
Maggio-Price and Dr. Iritani.

Current research suggests that inflammation increases the risk of plaque rupture in
atherosclerosis. The related report by Ovchinnikova et al, "T cell activation leads
to reduced collagen maturation in atherosclerotic plaques of ApoE-deficient- mice,"
appears in the February 2009 issue of The American Journal of Pathology. Atherosclerosis
is a disease of arterial blood vessels where fats, cholesterol, blood cells, and fibers
form hardened plaques on the artery wall. These plaques restrict blood flow to tissues
such as the heart and brain by narrowing the artery. Atherosclerosis can be caused by high
blood pressure, high fat and high cholesterol diets, smoking, and diabetes. People with
atherosclerotic plaques often show no symptoms for decades. Atherosclerotic plaques
consist of lipid cores covered by collagen fiber caps. These plaques can suddenly rupture,
resulting in blood clots that completely block blood flow and lead to heart attack or
stroke in otherwise healthy individuals. One potential cause of plaque rupture is the
thinning of the collagen fiber cap covering the plaque. Inflammatory cells are often
observed at the site of plaque rupture. Researchers led by Dr. GŲran K Hansson at the
Karolinska Institute explored the role of inflammatory cells in atherosclerotic plaque
rupture using an animal model of atherosclerosis with hyper-activated immune cells. They
found that inflammation leads to a reduction of mature collagen in atherosclerotic
plaques, leading to thinner caps that are more likely to rupture. They then identified a
collagen-maturing enzyme, lysyl-oxidase (LOX), which represents a novel target in
inflammation-induced plaque rupture.

Jefferson scientists discover a key
protein regulator of inflammation and cell death

Reporting in the journal Nature, researchers led by Emad Alnemri, Ph.D., professor of
Biochemistry and Molecular Biology in the Kimmel Cancer Center at Jefferson, discovered a
key protein component involved in inflammation. The protein, AIM2 (absent in melanoma 2),
is involved in the detection and reaction to dangerous cytoplasmic DNA that is produced by
infection with viral or microbial pathogens, or by tissue damage. AIM2 also appears to be
a tumor suppressor, and its inactivation may play a role in the development of cancer,
according to Dr. Alnemri. AIM2 belongs to a class of proteins called inflammasomes, which
are multi-protein complexes that play major roles as guardians against both viral and
bacterial infections. Inflammasomes also detect dangerous self-molecules associated with
tissue damage. According to Dr. Alnemri, when cells are infected with pathogens, AIM2
senses the presence of the pathogen's DNA in the cytoplasm. It then binds to the foreign
DNA and causes a rapid inflammatory reaction that sends a danger signal alerting the body
to the invading pathogen. When AIM2 binds to the foreign DNA, it recruits a cytoplasmic
protein called ASC. ASC and AIM2 then work together to activate caspase-1, a cysteine
protease involved in the production of interleukin1beta and other inflammatory cytokines
that cause inflammation.

Oregano doesnīt only give a Pizza its typical taste. Researchers at Bonn University and
the ETH ZŁrich have discovered that this spice also contains a substance which, amongst
other qualities, appears to help cure inflammations. The researchers administered its
active ingredient - known as beta-caryophyllin (E-BCP) - to mice with inflamed paws. In
seven out of ten cases there was a subsequent improvement in the symptoms. E-BCP might
possibly be of use against disorders such as osteoporosis and arteriosclerosis.

Metabolic syndrome is a pre-cursor to diabetes, coronary heart disease, and other serious
illnesses. Patients have long been advised to eat a low-fat diet even though carbohydrate
restriction has been found to be more effective at reducing specific markers, such as high
triglycerides. A new study indicates that a diet low in carbohydrates is also more
effective than a diet low in fat in reducing saturated fatty acids in the blood and
reducing markers of inflammation.

A new study, which appears today in the online edition of the European Heart Journal, has
found strong evidence that recent respiratory infections increase the risk of heart
attacks and strokes, both of which are more common in the winter.

Gene-expression profiles might be used to identify prognostic biomarkers for Kawasaki
disease, and help to unravel the underlying biology of the illness, research published
this week in the online open access journal Genome Biology reveals. The new findings also
support the idea that gene-expression profiles might be used to generate biomarkers for
other systemic inflammatory illnesses.

A study by Dr. Kitasato and colleagues demonstrated that cytokine stimulation induced iNOS
expression and NO generation, which was sufficient to cause DNA damage in normal hamster
gallbladder epithelial cells. These findings suggest that NO-mediated oxidative DNA damage
produced by inflammatory cytokines through iNOS expression is involved in an initiation
process that links chronic biliary inflammation to malignant transformation.

Inflammation is a rapid yet coordinated response that can lead to the destruction of
microbes and host tissue. Triggers capable of inducing an inflammatory response include
tissue damage and infection by pathogenic and nonpathogenic microbes. Each of these
triggers represents a qualitatively distinct stress to the host immune system, yet our
understanding of whether they are interpreted as such remains poor. Accumulating evidence
suggests that recognition of these distinct stimuli converges on many of the same
receptors of the innate immune system. Here I provide an overview of these innate
receptors and suggest that the innate immune system can interpret the context of an
inflammatory trigger and direct inflammation accordingly.

Researchers demonstrated for the first time a link between cell-death-inducing TRAIL's
receptor and cancer susceptibility. Unexpectedly, they also found a connection -- via
TRAIL -- between inflammation and cancer susceptibility.

With up to half of a persons body mass consisting of skeletal muscle, chronic
inflammation of those muscles  which include those found in the limbs  can
result in significant physical impairment. According to University of Illinois kinesiology
and community health professor Kimberly Huey, past research has demonstrated that the
antioxidant properties of Vitamin E may be associated with reduced expression of certain
pro-inflammatory cytokines, in vitro, in various types of cells. Cytokines are regulatory
proteins that function as intercellular communicators that assist the immune system in
generating a response. To consider whether the administration of Vitamin E, in vivo, might
have similar effects on skeletal and cardiac muscle, Huey and a team of Illinois
researchers put Vitamin E to the test in mice. The team included study designer Rodney
Johnson, a U. of I. professor of animal sciences, whose previous work has suggested a
possible link, in mice, between short-term Vitamin E supplementation and reduced
inflammation in the brain. The study represents the first time researchers have looked at
in vivo effects of Vitamin E administration on local inflammatory responses in skeletal
and cardiac muscle. In this study, the researchers investigated the effects of prior
administration of Vitamin E in mice that were then injected with a low dose of E. coli
lipopolysaccharide (LPS) to induce acute systemic inflammation. The effects were compared
with those found in placebo control groups.

Exhaled Nitric Oxide and Air Pollution
Airborne particles have been linked to pulmonary oxidative stress and inflammation.
Because these effects may be particularly great for traffic-related particles, Adar et al.
(p. 507) examined associations between particle exposures and exhaled nitric oxide (FeNO)
in a study of 44 senior citizens; this involved repeated trips aboard a diesel bus.
Samples of (FeNO) collected before and after the trips were regressed against
microenvironmental and ambient particle concentrations using mixed models controlling for
multiple variables. Fine particle exposures resulted in increased levels of (FeNO) in
participants, suggesting increased airway inflammation. These associations were best
assessed by microenvironmental exposure measurements during periods of high personal
particle exposures.

Fatty acid tied to depression and
inflammation
Specifically, the more omega-6 fatty acids people had in their blood compared with omega-3
fatty acid levels, the more likely they were to suffer from symptoms of depression and
have higher blood levels of inflammation-promoting compounds, report Dr. Janice K.
Kiecolt-Glaser and her colleagues from Ohio State University College of Medicine in
Columbus.

Research suggests fitness may reduce
inflammation
Although a number of studies have suggested that regular exercise reduces inflammation
 a condition that is predictive of cardiovascular and other diseases, such as
diabetes  its still not clear whether there is a definitive link. And if such
a link exists, the nature of the relationship is by no means fully understood. A recent
study by kinesiology and community health researchers at the University of Illinois
provides new evidence that may help explain some of the underlying biological mechanisms
that take place as the result of regular exercise. According to the researchers, that
knowledge could potentially lead to a better understanding of the relationship between
exercise and inflammation.

How diet, exercise and weight loss
affect inflammation
"We are finding that inflammation of the fat tissue causes both diabetes and heart
attacks," said Dr. Christie Ballantyne, director of the Center for Cardiovascular
Disease Prevention at the Methodist DeBakey Heart Center. "This study will examine
how diet, exercise and weight loss affect inflammation, and how these changes affect the
health of the patient's heart."

Connecting Diabetes And Inflammation
It has long been known that type 1 diabetes is an autoimmune disease. The body attacks the
islet cells in the pancreas that produce insulin. In recent years, the immune system has
also been implicated in type 2 diabetes  in particular imbalances in cytokines, an
immune system component that causes inflammation.

For Allergy & Immunology Researchers
Identify A Potential Role For Retinoic Acid In Autoimmune And Inflammatory Diseases
An important finding, which could eventually lead to a new therapeutic approach for
treating autoimmune and inflammatory diseases such as rheumatoid arthritis, colitis,
psoriasis and others, was announced today by researchers at the La Jolla Institute for
Allergy & Immunology (LIAI). The studies, conducted in laboratory mice, demonstrated
the role of retinoic acid, a substance derived when Vitamin A is broken down in the body,
in regulating inflammation.

New data on the probiotic strain
Bifantis shows anti-inflammatory properties
The biotechnology company Alimentary Health today announced results from two studies that
demonstrate the anti-inflammatory activity of a natural probiotic bacterial strain of
human origin, Bifantis (Bifidobacterium infantis 35624), in models of arthritis and
Salmonella infection. Data from these studies were presented this week at the 38th annual
Digestive Disease Week conference taking place in Washington D.C.

Belly fat may drive inflammatory
processes associated with disease
As scientists learn more about the key role of inflammation in diabetes and heart disease,
new research from Washington University School of Medicine in St. Louis suggests that fat
in the belly may be an important promoter of that inflammation. The researchers have
confirmed that fat cells inside the abdomen secrete molecules that increase inflammation.
This is the first evidence of a potential mechanistic link between abdominal fat and
systemic inflammation.

Resolvin E1 Protects against
Inflammation and Bone Loss in Experimental Periodontitis
Gum disease is initiated by bacteria populating dental plaque and may eventually result in
tissue and tooth loss. Gum disease is similar to other chronic inflammatory diseases such
as arthritis, where inflammation causes tissue damage and is responsible for the disease.
To date, the prevention of gum disease is limited to successful oral hygiene and regular
professional care. However, despite these preventive actions, plaque control is not enough
to prevent disease in susceptible individuals with a high inflammatory response.

Researchers presenting their findings today during the 35th Annual Meeting of the American
Association for Dental Research are introducing Resolvins, a new family of biologically
active products of omega-3 fatty acids. They are natural endogenous regulators of the
inflammatory response. Since it is now known that inflammation plays a critical role in
many diseases, including heart diseases and asthma, experiments were carried out to test
the actions of the newly described EPA (eicosapentanoic acid)-derived Resolvin E1 (RvE1)
in regulating tissue destruction and resolving inflammation in gum disease. Experimental
gum disease characterized by tissue inflammation and bone loss was stimulated in rabbits
by the application of specific bacteria that cause human gum disease. The results of this
study showed that topical application of RvE1 in experimental gum disease provided
remarkable protection against soft tissue and bone loss associated with gum disease
(periodontitis). Analysis of these data supports the concept that inflammation is a good
therapeutic target in the treatment of periodontal disease.

Harvard and U. Pittsburgh researchers
explain carbon monoxide's anti-inflammatory effects
In a study appearing in The FASEB Journal (April 2007), scientists from Harvard and the
University of Pittsburgh have shown for the first time that anti-inflammatory effects of
CO originate within cells' own molecular engines, mitochondria. Specifically, mitochondria
react to low levels of CO by releasing chemical signals that reduce or shut down the
body's inflammatory response, raising possibilities for development of new
anti-inflammatory therapies, one of which may be low levels of inhaled CO.

Omega-3 Fatty Acids in Inflammation and
Autoimmune Diseases
The anti-inflammatory properties of 3 fatty acids, especially EPA, are due to competition
with arachidonic acid (AA) as a substrate for cyclooxygenases and 5-lipoxygenase. The
eicosanoids from the 6 and 3 fatty acids have opposing properties. The eicosanoids are
considered a link between PUFA, inflammation and immunity. In addition to their effects on
prostaglandins, thromboxanes and leukotrienes, 3 fatty acids suppress the production on
interleukin 1 (IL-1Ŗ) by suppressing the IL-1Ŗ mRNA, as well as the expression of Cox2
(cytooxygenase) mRNA that is induced by IL-1Ŗ. Cox2 is overexpressed in colon cancer
cells. Both ALA, and EPA and DHA are involved in immune function. The precise effect of
ALA depends on the level of linoleic acid (LA) and total PUFA content of the diet.